Predomimantly tissue dwelling -> vastly higher levels in tissue than blood. They migrate into tissue from in response to cytokines.
[[Respiratory medicine MCQ discussion#Q 4: Allergic bronchopulmonary aspergillosis]]
There are several eosinophilic lung diseases
[[#Note on eosinophils|+ eosinophilia]]

Mucus plugs -> lung collapse
Recurrent episodes -> upper lobe fibrosis

Treatment: Systemic prednisilone; ICS will help asthma but not the lung infitrates.

All patients have resting or exercise induced hypoxia with increased [[Respiratory medicine MCQ discussion#Alveolar / arterial oxygen tension gradient|Alveolar arterial oxygen tension gradient]] (i.e reduced capacity for gas exchange)

• can be studied under inflammatory diarrhoeal causes and watery diarrhoeal causes.
  #2022GM Q21

Review of airway histology

Respiratory epithelium - ciliated pseudostratified columnar epithelium.

Note the presence of smooth muscle and it's decreasing thickness as the airways become smaller.

Bronchioles - intralobular airways < 1mm in diameter arising roughly after the 10th generation of branching.

Epidemiology

Commoner in women.
Increases with age; marked increase after 60 years.

Pathology

Bronchiectasis is the permanent dilation of bronchi and
bronchioles caused by destruction of the muscle and the
supporting elastic tissue, resulting from or associated with
chronic necrotizing infections. It is not a primary disease
but rather secondary to persisting infection or obstruction
caused by a variety of conditions

Obstructive impairment (ie, reduced or normal FVC, low FEV1, and low FEV1/FVC) is the most frequent finding on spirometry. ;
$$
\LARGE{Obstruction = ↓\frac{FEV_{1}}{FVC}}
$$

Morphology

Usually affects bilateral lower lobes.
Permanent dilation -> small airways are traceable almost upto the pleura. (in normal lungs, they stop about 2 cm short of the pleura)
Chronic inflammatory exudate is seen.
Extensive desquamation of epithelium causing ulceration.
Healing is usually by fibrosis.
Abscesses can form as complications.

Diagnosis:

Clinical and CT:
CT features that are reliable signs of bronchiectasis:

• Airway-to-arterial ratio ≥1.5 (internal airway lumen diameter/adjacent pulmonary artery diameter)
• Lack of tapering of bronchi (tram track appearance)
• Airway visibility within 1 cm of a costal pleural surface or touching the mediastinal pleura

Causes of bronchiectasis and basis of disease

Common causes

Obstruction - tumour, lymph nodes, aspiration etc. <- impaired drainage
Inherited disorders -
Cystic fibrosis <- impaired clearance of mucous
Kartagener syndrome <- Ciliary impairement
Autosomal recessive #autosomal-Recessive
Situs inversus, chronic sinusitis, and bronchiectasis; Underlying pathology is primary ciliary diskinesia. Kartagener Xn is a subset of primary ciliary diskinesia (in which patients may not have situs inversus).
Screening test -> patients have low levels of nasal nitric oxide.

Immunoglobulin deficiencies <- recurrent infection
Necrotizing of suppurative pneumonia - staph aureus or klebsiella <- scarring and impaired clearance; ?exagerrated neutrophil response

Other causes

Young syndrome - similar to CF but no evidence of CF; rare diagnosis nowadays.
Associated with two rheumatic disorders - Sjogren syndrome and Rheumamtoid arthritis.
[[General Medicine 1#Allergic bronchopulmonary aspergillosis|Allergic bronchopulmonary aspergillosis]]

Management

Antibiotics for exacerbations
Control of acute bleeding with bronchoscopic local therapy or bronchial artery embolization.
Refractory disease: surgical therapy - ? resection

Immunodeficiency syndromes

Primary immunodeficiencies arise from inborn defects. They usually present in childhood.
Common variable immunodeficiency is an notable exception to this.

Seconday immunodeficiency is far more common (?in adult populations)

• Diabetes mellitus
• Human immunodeficiency virus (HIV) infection
• Cirrhosis
• Nephrotic syndrome
• Other protein-losing states, such as enteropathies, severe exudative skin disease including burn injury, and peritoneal dialysis
• Malnutrition
• Hemoglobinopathy
• Inflammatory bowel disease or rheumatoid arthritis receiving immunosuppressive therapies (particularly tumor necrosis factor [TNF] inhibitors)
• Neurologic disease
• Autoimmune disease
• Splenectomy
• Malignancy
• Radiation therapy
• Immunosuppressive agents, such as glucocorticoids and others
• Immunomodulatory agents, such as rituximab, etanercept, and others

Typical presentations and associated defects in the immune system

Skin infections, in isolation, are not usually indicative of an underlying primary immunodeficiency.
 Recurrent abscess formation in the same anatomic location often arises from a local defect, such as a congenital branchial cleft cyst, pilonidal or urachal cyst, hidradenitis suppurativa, or a retained foreign body.
 Chronic mucocutaneous candidiasis - ussually begins in childhood; associated with several immunodeficiency states; usually doesn't show systemic infection with the fungus.
 Recurrent herpevirus infection / reactivation -> These individuals should be evaluated for underlying T or natural killer (NK) cell dysfunction.
 However, recurrent respiratory tract infections in combination with more serious infections are a classic presentation of antibody deficiencies.
 Isolated urinary tract infections are more suggestive of anatomic defect than immunodeficiency.
 Relapsing, recurrent, and/or progressive enterocolitis due to common enteropathogens, such as Giardia, enteroviruses, cytomegalovirus, and campylobacter, are associated with underlying hypogammaglobulinemia and/or T cell immunodeficiency.
 recurrent Neisseria meningitidis meningitis -> Deficiency of one or more of the terminal complement components (C5, C6, C7, C8, C9) . Low complement levels may be due to either congenital complement deficiency or acquired diseases, such as systemic lupus erythematosus.
 Immunoglobulin deficiency disorders or impaired reticuloendothelial function resulting from splenectomy or hemoglobinopathy are associated with an increased risk of bacteremia and meningitis due to encapsulated pathogens.
 Marked elevation of serum IgE with multisystem infections -> Job syndrome

Amyloidosis

Subtypes of amyloidosis

Other forms of amyloidosis:

• Heritable amyloidosis types
• Organ specific amyloidosis
• Dialysis related amyloidosis

Diagnosis

Histological : Fat pad biopsy (less risk of bleeding)
Organ biopsy is needed if a specific organ is involved.

See [[Respiratory medicine MCQ discussion#Mechanism of DLCO|mechanism of the test]] below
[[General Medicine 1#Allergic bronchopulmonary aspergillosis]]

[[Respiratory medicine MCQ discussion#Q 1 scleroderma]]